Immune modulation by rebamipide in a mouse model of Sjogren's syndrome via T and B cell regulation

Abstract

Rebamipide is a gastroprotective drug used widely in the treatment of gastritis and gastric ulcers. It has also been shown to improve dry eye and dry mouth, two major symptoms of Sjogren's syndrome (SS). However, little is known about the effects of rebamipide on T and B cell regulation in SS. In this study, we used a NOD/ShiLtJ mouse model of SS to examine the ability of rebamipide to ameliorate disease development by modulating T and B cells. Our results show that the oral administration of rebamipide suppressed SS progression and the level of inflammatory cytokines, including interleukin (IL)-6, tumor necrosis factor-α, and IL-17, in the salivary glands and spleen of NOD/ShiLtJ mice. Rebamipide treatment also increased the number of ex vivo CD19+CD25+Foxp3+ regulatory B cells and CD19+CD5+CD1d + IL-10+ cells in NOD/ShiLtJ mice. In vitro, rebamipide suppressed IL-6 and IL-17 production by Th17 cells in splenic CD4+ cells from the mice. Thus, rebamipide may be effective in controlling the immune imbalance between pathogenic immune cells and regulatory cells, resulting in fundamental improvement in patients with SS.

Keywords: IL-17-producing T cells; Rebamipide; Regulatory B cells; Sjogren’s syndrome.